77-OR: Native LDL Upregulate the NLRP3 Inflammasome in Human Adipose Tissue: A Mechanism for Higher Risk for Type 2 Diabetes in Subjects with HyperapoB
Bibliographic record
Abstract
Background and Hypothesis: Elevated plasma apoB-lipoproteins (hyperapoB, mostly LDL) predicts the incidence of type 2 diabetes (T2D) and its risk factors including systemic activation of the interleukin-1 system (measured as plasma IL-1 receptor antagonist, IL-1Ra) . Moreover, native LDL induce white adipose tissue (WAT) dysfunction. Underlying mechanisms for these findings remain unclear. Activation of WAT NLRP3 inflammasome and secretion of IL-1β promotes WAT dysfunction and related risk factors for T2D. We hypothesized that native LDL upregulate WAT NLRP3 inflammasome/IL-1β pathway. Methods: This data represents baseline analysis of a 3-month clinical trial with omega-3 fatty acid supplementation in nondiabetic men (N=13) and women (N=27) . We assessed insulin secretion and sensitivity by Botnia clamps, postprandial fat metabolism after a high-fat-meal (68% fat) , and priming and/or activation of NLRP3 inflammasome in subject hip WAT biopsies ex vivo using native LDL, lipopolysaccharides (LPS) (priming control) and/or ATP (activation control) . Results: Incubation of WAT with native LDL (1.2 g apoB/L) increased IL-1β secretion in ATP- but not LPS-treated WAT. Subjects with higher than median plasma apoB (1.23±0.15 g/L) had higher WAT IL-1β-secretion than those with lower apoB, using multiple combination of LDL, LPS and/or ATP, independent of adiposity, macronutrient intake or plasma lipids. WAT NLRP3 mRNA expression and IL-1β secretion correlated positively with hyperinsulinemia, insulin resistance, postprandial hypertriglyceridemia and hyperchylomicronemia and plasma IL-1Ra. Adjusting for sex and WAT IL-1β-secretion or sex and plasma IL-1Ra eliminated the association of plasma apoB with these risk factors (except hypertriglyceridemia) . Conclusion: Native LDL are priming signals of WAT NLRP3 inflammasome, which may explain higher risk for T2D in subjects with hyperapoB. ClinicalTrials.gov (NCT04496154) . Disclosure S.Bissonnette: None. V.Lamantia: None. Y.Cyr: None. M.Devaux: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc. M.Chretien: None. M.Saleh: None. M.Faraj: None. Funding Canadian Institutes of Health Research (CIHR) (FRN# 123409)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".